Artificial extracellular matrix composed of collagen I and highly sulfated hyaluronan interferes with TGFβ(1) signaling and prevents TGFβ(1)-induced myofibroblast differentiation

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

Abstract

Sulfated glycosaminoglycans are promising components for functional biomaterials since sulfate groups modulate the binding of growth factors and thereby influence wound healing. Here, we have investigated the influence of an artificial extracellular matrix (aECM) consisting of collagen I (coll) and hyaluronan (HA) or highly sulfated HA (hsHA) on dermal fibroblasts (dFb) with respect to their differentiation into myofibroblasts (MFb). Fibroblasts were cultured on aECM in the presence of aECM-adsorbed or soluble transforming growth factor β1 (TGFβ1). The synthesis of α-smooth muscle actin (αSMA), collagen and the ED-A splice variant of fibronectin (ED-A FN) were analyzed at the mRNA and protein levels. Furthermore, we investigated the bioactivity and signal transduction of TGFβ1 in the presence of aECM and finally made interaction studies of soluble HA or hsHA with TGFβ1. Artificial ECM composed of coll and hsHA prevents TGFβ1-stimulated αSMA, collagen and ED-A FN expression. Our data suggest an impaired TGFβ1 bioactivity and downstream signaling in the presence of aECM containing hsHA, shown by massively reduced Smad2/3 translocation to the nucleus. These data are explained by in silico docking experiments demonstrating the occupation of the TGFβ-receptor I binding site by hsHA. Possibly, HA sulfation has a strong impact on TGFβ1-driven differentiation of dFb and thus could be used to modulate the properties of biomaterials.

Details

OriginalspracheEnglisch
Seiten (von - bis)7775-86
Seitenumfang12
FachzeitschriftActa biomaterialia
Jahrgang9
Ausgabenummer8
PublikationsstatusVeröffentlicht - 18 Apr. 2013
Peer-Review-StatusJa

Externe IDs

Scopus 84891693365
ORCID /0000-0002-5611-9903/work/142244035

Schlagworte

Schlagwörter

  • Biomimetic Materials/chemistry, Cell Differentiation, Cells, Cultured, Collagen Type I/chemistry, Extracellular Matrix/chemistry, Humans, Hyaluronic Acid/chemistry, Materials Testing, Myofibroblasts/cytology, Signal Transduction/physiology, Sulfates/chemistry, Surface Properties, Transforming Growth Factor beta1/metabolism